All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
There are approximately 2,500 heart transplants performed every year. A significant obstacle to successful heart transplantation is the limited tolerated ischemia time of the heart to about six hours with currently available preservation methods and solutions. This time frame significantly restricts the size of the geographic region from which a donor organ can transported before the viability of the donor organ for transplantation is compromised. Graft quality also decreases with prolonged storage time, and various studies have shown that suboptimal quality of a heart during transplantation is associated with increased risk of organ rejection in the postoperative period.
A number of transplantation preservation solutions are known in the art. See, e.g., P. Michel et al., “A comparative study of the most widely used solutions for cardiac graft preservation during hypothermia,” J. Heart Lung Transplant., 21(9):1030-39 (2002). More than ten different preservation solutions are already in clinical use. Id. Moreover, there are several different solutions in use that are so-called “intracellular solutions.” Id. Examples of “intracellular solutions” include University of Wisconsin (e.g., “UW,” “Belzer™” or “Viaspan®”) solution, the most commonly-used formulation, histidine-tryptophan-ketoglutarate (e.g., “HTK,” “Bretschneider's” or “Custodiol®”) solution, Stanford (“STF”) solution, and Eurocollins (“EC”) solution. See, e.g., G. M. Collins, “What solutions are best? Overview of flush solutions,” Transplant. Proc., 29:3543-44 (1997), D. G. Stein et al., “Cardiac preservation in patients undergoing transplantation. A clinical trial comparing University of Wisconsin solution and Stanford solution,” J. Thorac. Cardiovasc. Surg., 102:657-665 (1991), and D. T. Hsu et al., “Quantitative effects of myocardial edema on the left ventricular pressure-volume relation. Influence of cardioplegia osmolarity over two hours of ischemia arrest,” J. Thorac. Cardiovasc. Surg., 106:651-657 (1993).
There is a need in the art for an improved cardiac transplantation solution. In particular, there is a need for a solution that enables the prolonged storage of an organ, such as a heart, for transplantation. By prolonging the tolerable ischemia time of an organ graft, the geographic region from which a donor organ can transported before the viability of the donor organ for transplantation is compromised may be markedly expanded. This, in turn, may improve organ transplantation quality and increase the number of potential donors.